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Brain Behav Immun. 2016 Oct;57:106-115. doi: 10.1016/j.bbi.2016.06.011. Epub 2016 Jun 16.

β2-Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer.

Author information

1
Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
2
Division of Cancer Surgery, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
3
School of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria 3010, Australia.
4
Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia; Cousins Center for PNI, UCLA Semel Institute, Jonsson Comprehensive Cancer Center, and UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095, USA. Electronic address: erica.sloan@monash.edu.

Abstract

Chronic stress accelerates metastasis - the main cause of death in cancer patients - through the activation of β-adrenoceptors (βARs). We have previously shown that β2AR signaling in MDA-MB-231(HM) breast cancer cells, facilitates invadopodia formation and invasion in vitro. However, in the tumor microenvironment where many stromal cells also express βAR, the role of β2AR signaling in tumor cells in metastasis is unclear. Therefore, to investigate the contribution of β2AR signaling in tumor cells to metastasis in vivo, we used RNA interference to generate MDA-MB-231(HM) breast cancer cells that are deficient in β2AR. β2AR knockdown in tumor cells reduced the proportion of cells with a mesenchymal-like morphology and, as expected, reduced tumor cell invasion in vitro. Conversely, overexpression of β2AR in low metastatic MCF-7 breast cancer cells induced an invasive phenotype. Importantly, we found that knockdown of β2AR in tumor cells significantly reduced the impact of stress on metastasis in vivo. These findings highlight a crucial role for β2AR tumor cell signaling in the adverse effects of stress on metastasis, and indicate that it may be necessary to block β2AR on tumor cells to fully control metastatic progression.

KEYWORDS:

Breast cancer; Chronic stress; Invasion; Metastasis; β(2)-Adrenoceptor

PMID:
27321906
PMCID:
PMC5060133
DOI:
10.1016/j.bbi.2016.06.011
[Indexed for MEDLINE]
Free PMC Article

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